Administration of 150 mg/Kg ip of phenylbutazone to male Sprague-Dawley rats produced a massive necrosis in renal cortex and papillae without causing cellular damage in liver. When the hepatic mixed-function oxidase system was induced by the pretreatment of rats with phenobarbital, necrosis occurred in liver but not in kidney. In contrast, pretreatment with 3-methyl cholanthrene did not shift the necrosis from the kidney to liver. The purpose of this study is to elucidate the biochemical mechanism underlying phenylbutazone toxicity.